The investigator-initiated, Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) Trial will test the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) is superior to current state-of-the-art pharmacologic therapy with either rate control or rhythm control drugs for reducing total mortality (primary endpoint) and decreasing the composite endpoint of total mortality, disabling stroke, serious bleeding and cardiac arrest (secondary endpoint) in patients with untreated or incompletely treated AF warranting therapy. Additional secondary endpoints will include AF recurrence and quality of life and cost effectiveness. The need for this trial arises out of 1) the rapidly increasing number of patients >60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy in multiple recent trials to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radiofrequency catheter ablation for AF without appropriate evidence-based validation, and 4) the resulting impact of AF on national health care costs. This 140-center mortality study will randomize 3000 patients over 3 years to a strategy of catheter ablation (n=1500) vs. state-of-the-art rate or rhythm control drug therapy (n=1500). Each patient will have 1) characteristics similar to AFFIRM patients (age >65, or <65 with >1 risk factor for stroke, 2) documented AF warranting treatment, and 3) eligibility for both catheter ablation and >2 anti-arrhythmic or >3 rate control drugs. Patients will be followed every 6 months for >2 yrs (median 3.5 yrs) and will undergo repeat trans-telephonic monitoring, Holter monitoring, and CT/MR studies to assess the impact of treatment. The primary and secondary endpoints will be examined in pts with paroxysmal, persistent, or permanent AF, without regard to age or underlying heart disease. With an anticipated 3.5 year mortality rate of >12% in drug treated patients, 1500 patients in each treatment arm will provide 90% power for detecting a 30% relative reduction in overall mortality and >90% power for detecting a 25% reduction in the composite secondary endpoint. The CABANA trial will disclose the role of medical and ablative therapies for an ever-escalating national healthcare dilemma, ascertain the cost and influence of therapy on quality of life, establish the impact of therapy on atrial morphology and function, and will help determine if AF is a modifiable risk factor for cardiovascular mortality. CABANA will be a landmark trial that will guide therapy and shape health care policy in the AF arena for years to come.